Eliseo Guallar
Eliseo Guallar
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Chair and Professor of the Department of Epidemiology
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Professional overview
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Dr. Guallar is an epidemiologist whose research is focused on the study of cardiovascular disease epidemiology and prevention, with an emphasis on evaluating the role of environmental and nutritional exposures in the development of cardiovascular disease. This research has made critically important and novel contributions to our understanding of risk factors for chronic disease both in the US and globally. He has published seminal articles and is a leading figure in an emerging field highlighting the risks of exposure to levels of metals previously considered safe for cardiovascular health. In addition to his work in toxic metals, Dr. Guallar has made important contributions to understanding the effects of certain micronutrients and vitamin supplements on cardiovascular disease risk and outcomes. Publications in this area were influential in changing consumer habits and attitudes towards these products. Much of this research has been funded by the National Institutes of Health, the Agency for Healthcare Research and Quality, the American Heart Association, the CDC, and other funders.
Dr. Guallar was the founding director of the Center for Clinical Epidemiology at the Samsung Medical Center and a lead investigator of the Kangbuk Samsung Cohort Study at the Kangbuk Samsung Hospital since its inception in 2010. Dr. Guallar has published over 500 research papers in peer-reviewed journals. He is also a Deputy Editor for Methods at the Annals of Internal Medicine and a past member and Chair of the Cancer, Heart, and Sleep Study Section at the National Institutes of Health.
Prior to teaching at NYU, Dr. Guallar was a Professor of Epidemiology and Medicine at the Johns Hopkins University Bloomberg School of Public Health and a core faculty member of the Welch Center for Prevention, Epidemiology, and Clinical Research at Johns Hopkins. In the Department of Epidemiology, Dr. Guallar was the Director of the Environmental and Occupational Area of Concentration and the Co-Director of the PhD Program. Dr. Guallar was also an adjunct Professor at the Department of Clinical Research Design and Evaluation of the Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, in Seoul, Korea.
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Education
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Diploma of English, Spanish Official School of Languages at Zaragoza (Escuela Oficial de Idiomas de Zaragoza), Zaragoza, SpainMD, University of Zaragoza, Zaragoza, SpainMPH, University of Minnesota, Minneapolis, MNDrPH, Harvard University, Boston, MA
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Honors and awards
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Six Honor Calls in the MD Program, University of Zaragoza School of Medicine (1981)Fellow of Spain’s Program of Training of Graduate Research of the Ministry of Education and Science, University of Zaragoza (1988)Fulbright Scholar, sponsored by Spain’s Ministry of Health and Consumer Affairs (1989)Faculty Innovation Award, Johns Hopkins University Bloomberg School of Public Health (2001)Scientist Development Award, American Heart Association (2002)Fellow of the American Heart Association, Council on Epidemiology and Prevention (2013)Advising, Mentoring, and Teaching Recognition Award 2014 – 2015, Johns Hopkins University Bloomberg School of Public Health (2015)High Impact Research Icon, University of Malaya (2015)
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Publications
Publications
Moderate-Intensity Statins Plus Ezetimibe vs. High-Intensity Statins After Coronary Revascularization: A Cohort Study
AbstractKim, J., Kang, D., Park, H., Kang, M., Choi, K. H., Park, T. K., Lee, J. M., Yang, J. H., Song, Y. B., Choi, J. H., Choi, S. H., Gwon, H. C., Guallar, E., Cho, J., & Hahn, J. Y. (n.d.).Publication year
2023Journal title
Cardiovascular Drugs and TherapyVolume
37Issue
1Page(s)
141-150AbstractPurpose: Whether moderate-intensity statins plus ezetimibe could be an alternative to high-intensity statins in patients with atherosclerotic cardiovascular disease is unclear. We compared the risk of adverse cardiovascular events in patients receiving moderate-intensity statins plus ezetimibe vs. high-intensity statins after a coronary revascularization procedure using data from a large cohort study. Method: Population-based cohort study using nationwide medical insurance data from Korea. Study participants (n = 20,070) underwent percutaneous coronary intervention or coronary artery bypass graft surgery between January 1, 2015, and December 31, 2016, and received moderate-intensity statins (atorvastatin 10–20 mg or rosuvastatin 5–10 mg) plus ezetimibe (n = 922) or high-intensity statins (atorvastatin 40–80 mg or rosuvastatin 20 mg; n = 19,148). The primary outcome was a composite of cardiovascular mortality, hospitalization for myocardial infarction (MI), hospitalization for stroke, or revascularization. Results: At 12 months, the incidence rates of the primary outcome were 138.0 vs. 154.0 per 1000 person-years in the moderate-intensity stains plus ezetimibe and the high-intensity statins group, respectively. The fully adjusted hazard ratio [HR] for the primary outcome was 1.11 (95% confidence interval [CI] 0.86–1.42; p = 0.43). The multivariable-adjusted HR for a composite of cardiovascular mortality, hospitalization for MI, or hospitalization for stroke was 1.05 (95% CI 0.74–1.47; p = 0.80). During follow-up, the proportion of patients maintaining their initial lipid-lowering therapy was significantly higher in the moderate-intensity statins plus ezetimibe group than in the high-intensity statins group. Conclusions: Patients undergoing a coronary revascularization procedure who received moderate-intensity statins plus ezetimibe showed similar rates of major adverse cardiovascular events as patients who received high-intensity statins.Multivariate longitudinal data for survival analysis of cardiovascular event prediction in young adults: insights from a comparative explainable study
AbstractNguyen, H. T., Vasconcellos, H. D., Keck, K., Reis, J. P., Lewis, C. E., Sidney, S., Lloyd-Jones, D. M., Schreiner, P. J., Guallar, E., Wu, C. O., Lima, J. A., & Ambale-Venkatesh, B. (n.d.).Publication year
2023Journal title
BMC Medical Research MethodologyVolume
23Issue
1AbstractBackground: Multivariate longitudinal data are under-utilized for survival analysis compared to cross-sectional data (CS - data collected once across cohort). Particularly in cardiovascular risk prediction, despite available methods of longitudinal data analysis, the value of longitudinal information has not been established in terms of improved predictive accuracy and clinical applicability. Methods: We investigated the value of longitudinal data over and above the use of cross-sectional data via 6 distinct modeling strategies from statistics, machine learning, and deep learning that incorporate repeated measures for survival analysis of the time-to-cardiovascular event in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. We then examined and compared the use of model-specific interpretability methods (Random Survival Forest Variable Importance) and model-agnostic methods (SHapley Additive exPlanation (SHAP) and Temporal Importance Model Explanation (TIME)) in cardiovascular risk prediction using the top-performing models. Results: In a cohort of 3539 participants, longitudinal information from 35 variables that were repeatedly collected in 6 exam visits over 15 years improved subsequent long-term (17 years after) risk prediction by up to 8.3% in C-index compared to using baseline data (0.78 vs. 0.72), and up to approximately 4% compared to using the last observed CS data (0.75). Time-varying AUC was also higher in models using longitudinal data (0.86–0.87 at 5 years, 0.79–0.81 at 10 years) than using baseline or last observed CS data (0.80–0.86 at 5 years, 0.73–0.77 at 10 years). Comparative model interpretability analysis revealed the impact of longitudinal variables on model prediction on both the individual and global scales among different modeling strategies, as well as identifying the best time windows and best timing within that window for event prediction. The best strategy to incorporate longitudinal data for accuracy was time series massive feature extraction, and the easiest interpretable strategy was trajectory clustering. Conclusion: Our analysis demonstrates the added value of longitudinal data in predictive accuracy and epidemiological utility in cardiovascular risk survival analysis in young adults via a unified, scalable framework that compares model performance and explainability. The framework can be extended to a larger number of variables and other longitudinal modeling methods. Trial registration: ClinicalTrials.gov Identifier: NCT00005130, Registration Date: 26/05/2000.Nonalcoholic Fatty Liver Disease Without Metabolic-associated Fatty Liver Disease and the Risk of Metabolic Syndrome
AbstractSinn, D. H., Kang, D., Choi, S. C., Hong, Y. S., Zhao, D., Guallar, E., Park, Y., Cho, J., & Gwak, G. Y. (n.d.).Publication year
2023Journal title
Clinical Gastroenterology and HepatologyVolume
21Issue
7Page(s)
1873-1880.e1AbstractBackground & Aims: Metabolic (dysfunction)-associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD). Some people fulfill diagnostic criteria of NAFLD but not MAFLD (NAFLD without MAFLD), but the clinical implications of NAFLD in these subjects is unknown. Methods: We followed cohort of 12,197 men and women 20 years of age or older without metabolic dysfunction (defined by MAFLD criteria), heavy alcohol use, chronic viral hepatitis, liver cirrhosis, or malignancy for their risk of incident metabolic syndrome defined by Adult Treatment Panel III criteria. Results: By design, none of the study participants had MAFLD at baseline. The prevalence of NAFLD among participants without metabolic dysfunction meeting MAFLD criteria and without significant alcohol intake was 7.6%. During 74,508 person-years of follow-up, 2179 participants developed metabolic syndrome. The fully adjusted hazard ratio for metabolic syndrome comparing participants with NAFLD to those without it was 1.61 (95% confidence interval, 1.42–1.83). The increased risk of incident metabolic syndrome associated with NAFLD persisted for all studied subgroups, and the association was stronger for those with increased waist circumference (P for interaction = .029) and those without elevated triglycerides levels (P for interaction = .047). Conclusion: In this large cohort, participants with NAFLD without MAFLD were at higher risk of developing metabolic syndrome compared to participants with no NAFLD and no MAFLD. Using MAFLD criteria may miss opportunities for early intervention in these subjects.Obesity paradox in patients with non-small cell lung cancer undergoing immune checkpoint inhibitor therapy
AbstractLee, J. H., Kang, D., Ahn, J. S., Guallar, E., Cho, J., & Lee, H. Y. (n.d.).Publication year
2023Journal title
Journal of Cachexia, Sarcopenia and MuscleVolume
14Issue
6Page(s)
2898-2907AbstractBackground: The obesity paradox in patients with advanced non-small cell lung cancer receiving immune checkpoint inhibitor therapy has been observed, but its underlying mechanism is not fully understood. We aimed to investigate whether body composition affects the prognostic impact of obesity, as determined by body mass index (BMI), on survival. Methods: This retrospective study evaluated the data collected from Asian patients who were treated with immune checkpoint inhibitors for advanced non-small cell lung cancer between October 2015 and October 2021. We used abdominal cross-sectional imaging to calculate the skeletal muscle and visceral fat indices (cm2/m2) by dividing the cross-sectional areas of the skeletal muscle and visceral fat by the height squared. Cox proportional-hazards regression was performed to determine the correlation between BMI according to the Asia-Pacific classification, body composition metrics and overall survival. Results: We analysed the data of 820 patients (630 men and 190 women, with a mean age of 64.3 years [standard deviation: 10.4 years]) and observed 572 (69.8%) deaths with the 1-year mortality rate of 0.58 (95% confidence interval, 0.55–0.62). Obese BMI was associated with longer overall survival, independent of clinical covariates (hazard ratio, 0.64; 95% confidence interval: 0.52–0.80). The prognostic value of obese BMI remained after additional adjustments for skeletal muscle index (hazard ratio, 0.68; 95% confidence interval, 0.53–0.87) or visceral fat index (hazard ratio, 0.54; 95% confidence interval: 0.41–0.70). No association was observed between sex and the impact of BMI on overall survival (P-value for interaction >0.05). Conclusions: In Asian patients with advanced non-small cell lung cancer who received immune checkpoint inhibitors, obese BMI was associated with favourable overall survival independent of skeletal muscle or visceral fat mass.Oxidative Stress and Cardiovascular Risk Factors: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
AbstractHeravi, A. S., Zhao, D., Michos, E. D., Doria De Vasconcellos, H., Ambale-Venkatesh, B., Lloyd-Jones, D., Schreiner, P. J., Reis, J. P., Shikany, J. M., Lewis, C. E., Ndumele, C. E., Guallar, E., Ouyang, P., Hoogeveen, R. C., Lima, J. A., Post, W. S., & Vaidya, D. (n.d.).Publication year
2023Journal title
AntioxidantsVolume
12Issue
3AbstractIntroduction—Oxidative stress is linked to cardiovascular diseases (CVD) and is suggested to vary by sex. However, few population-level studies have explored these associations and the majority comprise populations with advanced CVD. We assessed urinary isoprostane concentrations, a standard measure of oxidative stress, in a relatively young and healthy cohort, hypothesizing that higher oxidative stress is associated with an adverse cardiometabolic profile and female sex. Methods—Oxidative stress was measured in 475 women and 266 men, aged 48–55 years, from the Coronary Artery Risk Development in Young Adults (CARDIA) study using urinary 8-isoprostane (IsoP) and 2,3-dinor-8-isoprostane (IsoP-M). Multivariable-adjusted regression was used to evaluate cross-sectional associations. As secondary analysis, previously measured plasma F2-isoprostanes (plasma IsoP) from another CARDIA subset was similarly analyzed. Results—Mean (SD) ages for men and women were 52.1(2.3) and 52.2(2.2) years, respectively (p = 0.46), and 39% of the participants self-identified as Black (vs. White). Before adjustments, female sex was associated with higher median urinary IsoP (880 vs. 704 ng/g creatinine in men; p < 0.01) and IsoP m (1675 vs. 1284 ng/g creatinine in men; p < 0.01). Higher body mass index (BMI), high-density cholesterol (HDL-C), and triglycerides, current smoking, and less physical activity were associated with higher oxidative stress. Diabetes was not associated with urinary IsoP but was associated with lower IsoP m and plasma IsoP. Higher serum creatinine showed diverging associations with higher plasma and lower urinary isoprostane concentrations. Conclusions—Different isoprostane entities exhibit varying association patterns with CVD risk factors, and therefore are complementary, rather than interchangeable, in assessment of oxidative stress. Still, consistently higher isoprostanes among women, smokers, less active persons, and those with higher BMI and plasma triglycerides could reflect higher oxidative stress among these groups. While urinary isoprostanes are indexed to urinary creatinine due to variations in concentration, caution should be exercised when comparing groups with differing serum creatinine.Regression of nonalcoholic fatty liver disease is associated with reduced risk of incident diabetes: A longitudinal cohort study
AbstractSinn, D. H., Kang, D., Guallar, E., Choi, S. C., Hong, Y. S., Park, Y., Cho, J., & Gwak, G. Y. (n.d.).Publication year
2023Journal title
PloS oneVolume
18Issue
7AbstractObjective Non-alcoholic fatty liver disease (NAFLD) is potentially reversible. However, whether improvement of NAFLD leads to clinical benefits remains uncertain. We investigated the association between regression of NAFLD and the risk of incident diabetes in a longitudinal way. Methods A cohort of 11,260 adults who had NAFLD at in an initial exam, had the second evaluation for NAFLD status at 1~2 years from an initial exam were followed up for incident diabetes from 2001 and 2016. NAFLD was diagnosed with abdominal ultrasound. Results At baseline, NAFLD was regressed in 2,559 participants (22.7%). During 51,388 person-years of follow-up (median 4 years), 1,768 participants developed diabetes. The fully adjusted hazard ratio (HR) for incident diabetes in participants with regressed NAFLD compared to those with persistent NAFLD was 0.81 [95% confidence interval (CI) 0.72–0.92]. When assessed by NAFLD severity, among participants with a low NAFLD fibrosis score (NFS) (< -1.455), participants with regressed NAFLD had a lower risk of incident diabetes than those with persistent NAFLD (HR 0.77, 95% CI 0.68–0.88). However, in participants with an intermediate to high NFS (≥ -1.455), the risk of incident diabetes was not different between NAFLD regression and persistence groups (HR 1.12, 95% CI 0.82–1.51). Conclusions Regression of NAFLD was associated with decreased risk of incident diabetes compared to persistent NAFLD. However, the benefit was evident only for NAFLD patients with low NFS. This suggests that early intervention for NAFLD, before advanced fibrosis is present, may maximize the metabolic benefit from NAFLD regression.Reply
Sinn, D. H., Kang, D., Guallar, E., Cho, J., & Gwak, G. Y. (n.d.). In Clinical Gastroenterology and Hepatology (1–).Publication year
2023Volume
21Issue
9Page(s)
2435-2436Seeing the Positive in Negative Studies
Guallar, E., Goodman, S. N., Localio, A. R., Stephens-Shields, A. J., & Laine, C. (n.d.).Publication year
2023Journal title
Annals of internal medicineVolume
176Issue
4Page(s)
561-563Validation of the IASLC Residual Tumor Classification in Patients with Stage III-N2 Non-Small Cell Lung Cancer Undergoing Neoadjuvant Chemoradiotherapy Followed by Surgery
AbstractLee, J., Lee, J., Hong, Y. S., Lee, G., Kang, D., Yun, J., Jeon, Y. J., Shin, S., Cho, J. H., Choi, Y. S., Kim, J., Zo, J. I., Shim, Y. M., Guallar, E., Cho, J., & Kim, H. K. (n.d.).Publication year
2023Journal title
Annals of SurgeryVolume
277Issue
6Page(s)
E1355-E1363AbstractObjective: The aim of this study was to validate the International Association for the Study of Lung Cancer (IASLC) residual tumor classification in patients with stage III-N2 non-small cell lung cancer (NSCLC) undergoing neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by surgery. Background: As adequate nodal assessment is crucial for determining prognosis in patients with clinical N2 NSCLC undergoing nCCRT followed by surgery, the new classification may have better prognostic implications. Methods: Using a registry for thoracic cancer surgery at a tertiary hospital in Seoul, Korea, between 2003 and 2019, we analyzed 910 patients with stage III-N2 NSCLC who underwent nCCRT followed by surgery. We classified resections using IASLC criteria: complete (R0), uncertain (R[un]), and incomplete resection (R1/R2). Recurrence and mortality were compared using adjusted subdistribution hazard model and Cox-proportional hazards model, respectively. Results: Of the 96.3% (n = 876) patients who were R0 by Union for International Cancer Control (UICC) criteria, 34.5% (n = 3O2) remained R0 by IASLC criteria and 37.6% (n = 329) and 28% (n = 245) migrated to R(un) and R1, respectively. Most of the migration from UICC-R0 to lASLC-R(un) and IASLC-R1/R2 occurred due to inadequate nodal assessment (85.5%) and extracapsular nodal extension (77.6%), respectively. Compared to R0, the adjusted hazard ratios in R(un) and R1/R2 were 1.20 (95% confidence interval, 0.94-1.52), 1.50 (1.17-1.52) (P fortrend =.001) for recurrence and 1.18 (0.93-1.51) and 1.51 (1.17-1.96) for death (P for trend =.002). Conclusions: The IASLC R classification has prognostic relevance in patients with stage III-N2 NSCLC undergoing nCCRT followed by surgery. The IASLC classification will improve the thoroughness of intraoperative nodal assessment and the completeness of resection.Vasomotor and other menopause symptoms and the prevalence of ideal cardiovascular health metrics among premenopausal stage women
AbstractChoi, H. R., Chang, Y., Kim, Y., Cho, Y., Kwon, M. J., Kang, J., Kwon, R., Lim, G. Y., Kim, K. H., Kim, H., Hong, Y. S., Park, J., Zhao, D., Cho, J., Guallar, E., Park, H. Y., & Ryu, S. (n.d.).Publication year
2023Journal title
MenopauseVolume
30Issue
7Page(s)
750-757AbstractObjective We examined the association between menopause symptoms and the prevalence of ideal cardiovascular health (CVH) metrics among premenopausal women. Methods This cross-sectional study comprised 4,611 premenopausal women aged 42 to 52 years. Data for CVH metrics were collected during health screening examinations. Menopause symptoms were measured using the Korean version of the Menopause-Specific Quality of Life questionnaire. For vasomotor, psychosocial, physical, and sexual symptoms, participants were divided into absent or symptomatic groups, further divided into tertiles (range, 0-7; 7 being the most bothersome). Ideal CVH metrics were defined according to the American Heart Association Life Simple 7 metrics, except dietary component. Cardiovascular health metrics were scored from 0 (unhealthy) to 6 (healthy) and classified as poor (0-2), intermediate (3-4), and ideal (5-6). Multinomial logistic regression models were used to estimate the prevalence ratios for intermediate and poor CVH metrics using ideal CVH as the reference. Results The overall and 4 menopause-specific quality of life domain scores were significantly associated with poorer CVH metrics scores in a dose-response manner (P < 0.05). After adjusting for age, parity, education level, anti-Mullerian hormone levels, and alcohol intake, women with the most bothersome degree for vasomotor, psychosocial, physical, and sexual symptoms had significantly higher prevalence of poor CVH metrics, with corresponding prevalence ratios (95% confidence interval) of 2.90 (1.95-4.31), 2.07 (1.36-3.15), 3.01 (1.19-7.65), and 1.66 (1.15-2.39), respectively, compared with those without each vasomotor, psychosocial, physical, and sexual symptom. Conclusions Premenopausal stage women with either vasomotor or nonvasomotor menopausal symptoms have significantly higher prevalence of poor CVH metrics, compared with those without any menopausal symptoms.Whole-exome sequencing in 415,422 individuals identifies rare variants associated with mitochondrial DNA copy number
AbstractPillalamarri, V., Shi, W., Say, C., Yang, S., Lane, J., Guallar, E., Pankratz, N., & Arking, D. E. (n.d.).Publication year
2023Journal title
Human Genetics and Genomics AdvancesVolume
4Issue
1AbstractInter-individual variation in the number of copies of the mitochondrial genome, called mitochondrial DNA copy number (mtDNA-CN), reflects mitochondrial function and has been associated with various aging-related diseases. We examined 415,422 exomes of self-reported White ancestry individuals from the UK Biobank and tested the impact of rare variants, at the level of single variants and through aggregate variant-set tests, on mtDNA-CN. A survey across nine variant sets tested enrichment of putatively causal variants and identified 14 genes at experiment-wide significance and three genes at marginal significance. These included associations at known mtDNA depletion syndrome genes (mtDNA helicase TWNK, p = 1.1 × 10−30; mitochondrial transcription factor TFAM, p = 4.3 × 10−15; mtDNA maintenance exonuclease MGME1, p = 2.0 × 10−6) and the V617F dominant gain-of-function mutation in the tyrosine kinase JAK2 (p = 2.7 × 10−17), associated with myeloproliferative disease. Novel genes included the ATP-dependent protease CLPX (p = 8.4 × 10−9), involved in mitochondrial proteome quality, and the mitochondrial adenylate kinase AK2 (p = 4.7 × 10−8), involved in hematopoiesis. The most significant association was a missense variant in SAMHD1 (p = 4.2 × 10−28), found on a rare, 1.2-Mb shared ancestral haplotype on chromosome 20. SAMHD1 encodes a cytoplasmic host restriction factor involved in viral defense response and the mitochondrial nucleotide salvage pathway, and is associated with Aicardi-Goutières syndrome 5, a childhood encephalopathy and chronic inflammatory response disorder. Rare variants were enriched in Mendelian mtDNA depletion syndrome loci, and these variants implicated core processes in mtDNA replication, nucleoid structure formation, and maintenance. These data indicate that strong-effect mutations from the nuclear genome contribute to the genetic architecture of mtDNA-CN.A metabolomics approach identified toxins associated with uremic symptoms in advanced chronic kidney disease
AbstractHu, J. R., Myint, L., Levey, A. S., Coresh, J., Inker, L. A., Grams, M. E., Guallar, E., Hansen, K. D., Rhee, E. P., & Shafi, T. (n.d.).Publication year
2022Journal title
Kidney InternationalVolume
101Issue
2Page(s)
369-378AbstractUremic symptoms are common in patients with advanced chronic kidney disease, but the toxins that cause these symptoms are unknown. To evaluate this, we performed a cross-sectional study of the 12 month post-randomization follow-up visit of Modification of Diet in Renal Disease (MDRD) participants reporting uremic symptoms who also had available stored serum. We quantified 1,163 metabolites by liquid chromatography-tandem mass spectrometry. For each uremic symptom, we calculated a score as the severity multiplied by the number of days the symptom was experienced. We analyzed the associations of the individual symptom scores with metabolites using linear models with empirical Bayesian inference, adjusted for multiple comparisons. Among 695 participants, the mean measured glomerular filtration rate (mGFR) was 28 mL/min/1.73 m2. Uremic symptoms were more common in the subgroup of 214 patients with an mGFR under 20 mL/min/1.73 m2 (mGFR under 20 subgroup) than in the full group. For all metabolites with significant associations, the direction of the association was concordant in the full group and the subgroup. For gastrointestinal symptoms (bad taste, loss of appetite, nausea, and vomiting), eleven metabolites were associated with symptoms. For neurologic symptoms (decreased alertness, falling asleep during the day, forgetfulness, lack of pep and energy, and tiring easily/weakness), seven metabolites were associated with symptoms. Associations were consistent across sensitivity analyses. Thus, our proof-of-principle study demonstrates the potential for metabolomics to understand metabolic pathways associated with uremic symptoms. Larger, prospective studies with external validation are needed.Adherence to Diet and Meal Timing in a Randomized Controlled Feeding Study of Time‐Restricted Feeding
AbstractWu, B., White, K., Maw, M. T. T., Charleston, J., Zhao, D., Guallar, E., Appel, L. J., Clark, J. M., Maruthur, N. M., & Pilla, S. J. (n.d.).Publication year
2022Journal title
NutrientsVolume
14Issue
11AbstractAdherence is critical in feeding studies to determine the efficacy of dietary interventions. This time‐restricted intake of meals (TRIM) investigation was a controlled feeding study that randomized 41 participants to follow 12 weeks of time‐restricted feeding (TRF) or a usual feeding pattern (UFP). Adherence was optimized through careful screening and participant orientation, flexibility in beverages and seasonings, and frequent contact between participants and staff. Adherence was measured daily using a self‐administered diary form. We calculated the percentage of participant‐days with perfect adherence to meal timing (ate all meals within their designated time window) and to food consumption (ate all study food and no non‐study food). Adherence was compared between study arms, days of the week, and weeks of the study period using generalized estimating equations (GEE) regression. There was perfect adherence to meal timing on 87% of participant‐days and to food consumption on 94% of participant-days, with no significant difference by arm. In UFP, but not TRF, participants had lower adherence to meal timing over the weekend (p‐value = 0.002) and during the first two weeks of intervention (p‐value = 0.03). A controlled feeding study randomizing free‐living individuals to different meal timings achieved a high degree of adherence to meal timing and food consumption, utilizing multiple strategies.Alcohol Consumption Patterns and Risk of Early-Onset Vasomotor Symptoms in Premenopausal Women
AbstractKwon, R., Chang, Y., Kim, Y., Cho, Y., Choi, H. R., Lim, G. Y., Kang, J., Kim, K. H., Kim, H., Hong, Y. S., Park, J., Zhao, D., Rampal, S., Cho, J., Guallar, E., Park, H. Y., & Ryu, S. (n.d.).Publication year
2022Journal title
NutrientsVolume
14Issue
11AbstractThe role of alcohol consumption in the risk of vasomotor symptoms (VMS), the most cardinal climacteric symptoms, is not well established. We examined their relationship with early-onset VMS among premenopausal women. Moderately-to-severely bothersome VMS, the primary outcome, was assessed using the Korean version of the Menopause-Specific Quality of Life questionnaire. The alcohol consumption categories included lifetime abstainer, former drinker, or current drinker, categorized as light, moderate, heavy, and very heavy. Compared with the lifetime-abstinence (reference), the multivariable-adjusted odds ratio (95% CIs) for prevalent VMS in alcohol consumption of <10, 10–19, 20–39, and ≥40 g/day were 1.42 (1.02–1.99), 1.99 (1.27–3.12), 2.06 (1.19–3.57), and 3.52 (1.72–7.20), respectively (p trend <0.01). Compared with the lifetime-abstinence, the multivariable-adjusted hazard ratios (95% CIs) for incident bothersome VMS among average alcohol consumption of <10, 10–19, 20–39, and ≥40 g/day were 1.10 (0.85–1.41), 1.03 (0.70–1.51), 1.72 (1.06–2.78), and 2.22 (1.16–4.23), respectively (p trend = 0.02). Increased alcohol consumption positively and consistently showed a relationship with increased risk of both prevalent and incident early-onset VMS. Refraining from alcohol consumption may help prevent bothersome VMS in premenopausal women.Assessing the Accuracy of Estimated Lipoprotein(a) Cholesterol and Lipoprotein(a)-Free Low-Density Lipoprotein Cholesterol
AbstractZheng, W., Chilazi, M., Park, J., Sathiyakumar, V., Donato, L. J., Meeusen, J. W., Lazo, M., Guallar, E., Kulkarni, K. R., Jaffe, A. S., Santos, R. D., Toth, P. P., Jones, S. R., & Martin, S. S. (n.d.).Publication year
2022Journal title
Journal of the American Heart AssociationVolume
11Issue
2AbstractBACKGROUND: Accurate measurement of the cholesterol within lipoprotein(a) (Lp[a]-C) and its contribution to low-density lipo-protein cholesterol (LDL-C) has important implications for risk assessment, diagnosis, and treatment of atherosclerotic cardiovascular disease, as well as in familial hypercholesterolemia. A method for estimating Lp(a)-C from particle number using fixed conversion factors has been proposed (Lp[a]-C from particle number divided by 2.4 for Lp(a) mass, multiplied by 30% for Lp[a]-C). The accuracy of this method, which theoretically can isolate “Lp(a)-free LDL-C,” has not been validated. METHODS AND RESULTS: In 177 875 patients from the VLDbL (Very Large Database of Lipids), we compared estimated Lp(a)-C and Lp(a)-free LDL-C with measured values and quantified absolute and percent error. We compared findings with an analo-gous data set from the Mayo Clinic Laboratory. Error in estimated Lp(a)-C and Lp(a)-free LDL-C increased with higher Lp(a)-C values. Median error for estimated Lp(a)-C <10 mg/dL was −1.9 mg/dL (interquartile range, −4.0 to 0.2); this error increased lin-early, overestimating by +30.8 mg/dL (interquartile range, 26.1– 36.5) for estimated Lp(a)-C ≥50 mg/dL. This error relationship persisted after stratification by overall high-density lipoprotein cholesterol and high-density lipoprotein cholesterol subtypes. Similar findings were observed in the Mayo cohort. Absolute error for Lp(a)-free LDL-C was +2.4 (interquartile range, −0.6 to 5.3) for Lp(a)-C<10 mg/dL and −31.8 (interquartile range, −37.8 to −26.5) mg/dL for Lp(a)-C≥50 mg/dL. CONCLUSIONS: Lp(a)-C estimations using fixed conversion factors overestimated Lp(a)-C and subsequently underestimated Lp(a)-free LDL-C, especially at clinically relevant Lp(a) values. Application of inaccurate Lp(a)-C estimations to correct LDL-C may lead to undertreatment of high-risk patients.Association Between Retinopathy of Prematurity in Very-Low-Birth-Weight Infants and Neurodevelopmental Impairment
AbstractHan, G., Lim, D. H., Kang, D., Cho, J., Guallar, E., Chang, Y. S., Chung, T. Y., Kim, S. J., & Park, W. S. (n.d.).Publication year
2022Journal title
American Journal of OphthalmologyVolume
244Page(s)
205-215AbstractPurpose: To evaluate the impact of retinopathy of prematurity (ROP) severity and the treatment of very-low-birth-weight infants (VLBWIs) on neurodevelopmental impairment in early childhood. Design: Prospective cohort study. Method: This was a prospective cohort study. The data were obtained from the Korean Neonatal Network (KNN), a nationwide registry for VLBWIs. Infants who were born from 2013 to 2015 and underwent ROP evaluation at birth and neurodevelopmental examinations at corrected ages of 18 to 24 months were included in the study. Infants with a history of meningitis or severe congenital anomalies were excluded. The VLBWI patients were grouped into no ROP, no treatment-requiring ROP (non−TR-ROP), and treatment-requiring ROP (TR-ROP) groups. Neurodevelopmental impairment was defined as participants who had at least 1 developmental problem according to the Bayley Scales of Infant and Toddler Development−2nd Edition (Bayley-II; <70), Bayley Scales of Infant and Toddler Development−3rd Edition (Bayley-III; <70), and Korean Developmental Screening Test (K-DST) tests (below −1 SD), and the Korean Ages and Stages Questionnaire (K-ASQ) (below the threshold) and Gross Motor Function Classification System (GMFCS; at level 2 or above). Multivariable logistic regression analysis was performed to evaluate the association between ROP and neurodevelopmental impairment. Result: Among 3132 infants, 1093 (34.9%) had ROP. Among the ROP infants, 644 were not treated for ROP (non-TR-ROP group) and 449 received ROP treatments (TR-ROP group). The patients in the TR-ROP group had an increased risk of developing neurodevelopmental problems compared to those in the no ROP group (odds ratio [OR] = 1.72, 95% CI = 1.33-2.21). The TR-ROP group had a higher risk of all 3 types of neurodevelopmental problems: mental (OR = 1.62, 95% CI = 1.25-2.09), social (OR = 1.62, 95% CI = 1.12-2.09), and motor (OR = 1.69, 95% CI = 1.31-2.18). The risk of neurodevelopmental problems in patients treated with laser therapy did not differ from that in patients treated with anti−vascular endothelial growth factor (anti-VEGF) therapy (OR = 1.17, 95% CI = 0.73-1.88). Conclusion: ROP was independently associated with neurodevelopmental impairment in early childhood. The type of ROP treatment (anti-VEGF or laser treatment) did not affect neurodevelopmental impairment in patients in the TR-ROP group.Associations between aflatoxin B1-albumin adduct levels with metabolic conditions in Guatemala: A cross-sectional study
AbstractAlvarez, C. S., Rivera-Andrade, A., Kroker-Lobos, M. F., Florio, A. A., Smith, J. W., Egner, P. A., Freedman, N. D., Lazo, M., Guallar, E., Dean, M., Graubard, B. I., Ramírez-Zea, M., McGlynn, K. A., & Groopman, J. D. (n.d.).Publication year
2022Journal title
Health Science ReportsVolume
5Issue
1AbstractBackground and Aims: Metabolic conditions such as obesity, type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) are highly prevalent in Guatemala and increase the risk for a number of disorders, including hepatocellular carcinoma (HCC). Aflatoxin B1 (AFB1) levels are also notably elevated in the population and are known to be associated with HCC risk. Whether AFB1 also contributes to the high prevalence of the metabolic disorders has not been previously examined. Therefore, the purpose of this study was to assess the association between AFB1 and the metabolic conditions. Methods: Four-hundred twenty-three individuals were included in the study, in which AFB1-albumin adduct levels were measured in sera. Metabolic conditions included diabetes, obesity, central obesity, metabolic syndrome, and NAFLD. Crude and adjusted prevalence odds ratios (PORs) and 95% confidence intervals (95% CI) were estimated for the associations between the metabolic conditions and AFB1-albumin adduct levels categorized into quartiles. Results: The study found a significant association between AFB1-albumin adduct levels and diabetes (Q4 vs Q1 POR = 3.74, 95%CI: 1.71-8.19; P-trend.003). No associations were observed between AFB1-albumin adduct levels and the other conditions. Conclusions: As diabetes is the metabolic condition most consistently linked to HCC, the possible association between AFB1 exposure and diabetes may be of public health importance. Further studies are warranted to replicate the findings and examine potential mechanisms.Circulating bile acid concentrations and non-alcoholic fatty liver disease in Guatemala
AbstractRivera-Andrade, A., Petrick, J. L., Alvarez, C. S., Graubard, B. I., Florio, A. A., Kroker-Lobos, M. F., Parisi, D., Freedman, N. D., Lazo, M., Guallar, E., Groopman, J. D., Ramirez-Zea, M., & McGlynn, K. A. (n.d.).Publication year
2022Journal title
Alimentary Pharmacology and TherapeuticsVolume
56Issue
2Page(s)
321-329AbstractBackground: Non-alcoholic fatty liver disease (NAFLD) is a major liver disease worldwide. Bile acid dysregulation may be a key feature in its pathogenesis and progression. Aims: To characterise the relationship between bile acid levels and NAFLD at the population level. Methods: We conducted a cross-sectional study in Guatemala in 2016 to examine the prevalence of NAFLD. Participants (n = 415) completed questionnaires, donated blood samples and had a brief medical exam. NAFLD was determined by calculation of the fatty liver index. The levels of 15 circulating bile acids were determined by LC–MS/MS. Adjusted prevalence odds ratios (PORadj) and 95% CI were calculated to examine the relationships between bile acid levels (in tertiles) and NAFLD. Results: Persons with NAFLD had significantly higher levels of the conjugated primary bile acids glycocholic acid (GCA) (PORadj T3 vs T1 = 1.85), taurocholic acid (TCA) (PORadj T3 vs T1 = 2.45) and taurochenodeoxycholic acid (TCDCA) (PORadj T3 vs T1 = 2.10), as well as significantly higher levels the unconjugated secondary bile acid, deoxycholic acid (DCA) (PORadj T3 vs T1 = 1.78) and its conjugated form, taurodeoxycholic acid (TDCA) (PORadj T3 vs T1 = 1.81). Conclusions: The bile acid levels of persons with and without NAFLD differed significantly. Among persons with NAFLD, higher levels of the conjugated forms of CA (i.e. GCA, TCA) and the secondary bile acids that derive from CA (i.e. DCA, TDCA) may indicate there is hepatic overproduction of CA, which may affect the liver via aberrant signalling mediated by the bile acids.Comparing the Value of Data Visualization Methods for Communicating Harms in Clinical Trials
AbstractQureshi, R., Chen, X., Goerg, C., Mayo-Wilson, E., Dickinson, S., Golzarri-Arroyo, L., Hong, H., Phillips, R., Cornelius, V., DeMarco, M. M. A., Guallar, E., & Li, T. (n.d.).Publication year
2022Journal title
Epidemiologic ReviewsVolume
44Issue
1Page(s)
55-66AbstractIn clinical trials, harms (i.e., adverse events) are often reported by simply counting the number of people who experienced each event. Reporting only frequencies ignores other dimensions of the data that are important for stakeholders, including severity, seriousness, rate (recurrence), timing, and groups of related harms. Additionally, application of selection criteria to harms prevents most from being reported. Visualization of data could improve communication of multidimensional data. We replicated and compared the characteristics of 6 different approaches for visualizing harms: dot plot, stacked bar chart, volcano plot, heat map, treemap, and tendril plot. We considered binary events using individual participant data from a randomized trial of gabapentin for neuropathic pain. We assessed their value using a heuristic approach and a group of content experts. We produced all figures using R and share the open-source code on GitHub. Most original visualizations propose presenting individual harms (e.g., dizziness, somnolence) alone or alongside higher level (e.g., by body systems) summaries of harms, although they could be applied at either level. Visualizations can present different dimensions of all harms observed in trials. Except for the tendril plot, all other plots do not require individual participant data. The dot plot and volcano plot are favored as visualization approaches to present an overall summary of harms data. Our value assessment found the dot plot and volcano plot were favored by content experts. Using visualizations to report harms could improve communication. Trialists can use our provided code to easily implement these approaches.Editorial: higher levels of certain serum bile acids in non-alcoholic fatty liver disease–new insights from Guatemala.Authors’ reply
Rivera-Andrade, A., Petrick, J. L., Alvarez, C. S., Graubard, B. I., Florio, A. A., Kroker-Lobos, M. F., Parisi, D., Freedman, N. D., Lazo, M., Guallar, E., Groopman, J. D., Ramirez-Zea, M., & McGlynn, K. A. (n.d.).Publication year
2022Journal title
Alimentary Pharmacology and TherapeuticsVolume
56Issue
2Page(s)
361-362Efficacy of a tailored moisturizer for reducing chemotherapy-induced skin dryness in breast cancer patients: A randomized controlled clinical trial
Kang, D., Kim, N., Im, Y. H., Park, Y. H., Kim, J. Y., Park, H., Kim, E., Zhao, D., Guallar, E., Ahn, J. S., & Cho, J. (n.d.).Publication year
2022Journal title
Journal of the American Academy of DermatologyVolume
87Issue
4Page(s)
858-860Frequency of the PNPLA3 rs738409 polymorphism and other genetic loci for liver disease in a Guatemalan adult population
Lazo, M., Xie, J., Alvarez, C. S., Parisi, D., Yang, S., Rivera-Andrade, A., Kroker-Lobos, M. F., Groopman, J. D., Guallar, E., Ramirez-Zea, M., Arking, D. E., & McGlynn, K. A. (n.d.). In Liver International (1–).Publication year
2022Volume
42Issue
6Page(s)
1470-1474Harms in Systematic Reviews Paper 2: Methods used to assess harms are neglected in systematic reviews of gabapentin
AbstractQureshi, R., Mayo-Wilson, E., Rittiphairoj, T., McAdams-DeMarco, M., Guallar, E., & Li, T. (n.d.).Publication year
2022Journal title
Journal of Clinical EpidemiologyVolume
143Page(s)
212-223AbstractObjective: We compared methods used with current recommendations for synthesizing harms in systematic reviews and meta-analyses (SRMAs) of gabapentin. Study Design & Setting: We followed recommended systematic review practices. We selected reliable SRMAs of gabapentin (i.e., met a pre-defined list of methodological criteria) that assessed at least one harm. We extracted and compared methods in four areas: pre-specification, searching, analysis, and reporting. Whereas our focus in this paper is on the methods used, Part 2 examines the results for harms across reviews. Results: We screened 4320 records and identified 157 SRMAs of gabapentin, 70 of which were reliable. Most reliable reviews (51/70; 73%) reported following a general guideline for SRMA conduct or reporting, but none reported following recommendations specifically for synthesizing harms. Across all domains assessed, review methods were designed to address questions of benefit and rarely included the additional methods that are recommended for evaluating harms. Conclusion: Approaches to assessing harms in SRMAs we examined are tokenistic and unlikely to produce valid summaries of harms to guide decisions. A paradigm shift is needed. At a minimal, reviewers should describe any limitations to their assessment of harms and provide clearer descriptions of methods for synthesizing harms.Harms in Systematic Reviews Paper 3: Given the same data sources, systematic reviews of gabapentin have different results for harms
AbstractQureshi, R., Mayo-Wilson, E., Rittiphairoj, T., McAdams-DeMarco, M., Guallar, E., & Li, T. (n.d.).Publication year
2022Journal title
Journal of Clinical EpidemiologyVolume
143Page(s)
224-241AbstractObjective: In this methodologic study (Part 2 of 2), we examined the overlap in sources of evidence and the corresponding results for harms in systematic reviews for gabapentin. Study Design & Setting: We extracted all citations referenced as sources of evidence for harms of gabapentin from 70 systematic reviews, as well as the harms assessed and numerical results. We assessed consistency of harms between pairs of reviews with a high degree of overlap in sources of evidence (>50%) as determined by corrected covered area (CCA). Results: We found 514 reports cited across 70 included reviews. Most reports (244/514, 48%) were not cited in more than one review. Among 18 pairs of reviews, we found reviews had differences in which harms were assessed and their choice to meta-analyze estimates or present descriptive summaries. When a specific harm was meta-analyzed in a pair of reviews, we found similar effect estimates. Conclusion: Differences in harms results across reviews can occur because the choice of harms is driven by reviewer preferences, rather than standardized approaches to selecting harms for assessment. A paradigm shift is needed in the current approach to synthesizing harms.High low-density lipoprotein cholesterol level is associated with an increased risk of incident early-onset vasomotor symptoms
AbstractChoi, H. R., Chang, Y., Kim, Y., Kang, J., Kwon, M. J., Kwon, R., Lim, G. Y., Kim, K. H., Kim, H., Hong, Y. S., Zhao, D., Cho, J., Guallar, E., Park, H. Y., & Ryu, S. (n.d.).Publication year
2022Journal title
Scientific reportsVolume
12Issue
1AbstractWe investigated the associations between serum lipid profiles and risk of early-onset vasomotor symptoms (VMSs) in premenopausal women. This cohort study comprised 2,540 premenopausal women aged 42–52 years without VMSs at baseline (median follow-up: 4.4 years). VMSs, including hot flashes and night sweats, were assessed using the Menopause-Specific Quality of Life questionnaire (Korean version). Early-onset VMSs were defined as VMSs that occurred premenopause; moderate/severe VMSs were defined as a score of ≥ 3 points (range: 0 to 6, 6 being most bothersome). Cox proportional hazard regression models were used to estimate hazard ratios with 95% confidence intervals (CI) for the development of VMSs across the lipid levels. Higher low-density lipoprotein (LDL) cholesterol levels were positively associated with increased risk of early-onset VMSs. Compared to the < 100 mg/dL LDL group, the multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for incident VMSs were 1.19 (1.03–1.37) and 1.20 (1.03–1.40) in participants with LDL cholesterol levels of 100–129 mg/dL and ≥ 130 mg/dL, respectively (P for trend = 0.027). The multivariable-adjusted HR for incident moderate/severe VMSs was 1.37 (95% CI: 1.08–1.73) in participants with LDL ≥ 130 mg/dL, compared to those with LDL < 100 mg/dL. Meanwhile, triglycerides and total and high-density lipoprotein cholesterol levels were not significantly associated with early-onset VMSs risk in premenopausal women. Premenopausal women with high serum LDL cholesterol concentrations had a higher risk of incident early-onset VMSs. Further studies should confirm our findings and examine whether LDL-lowering interventions reduce the risk of early-onset VMSs among women during menopause transition.